This proposal seeks to renew Research Career Scientist Award held by Dr. Shyam S Mohapatra at the James A. Haley VA Hospital in Tampa, Florida since 2007. He is a Distinguished Health Professor and the Director of the Division of Translational Medicine- Center for Research and Education in Nanobioengineering at the VA-affiliated academic center- the University of South Florida. He is recognized nationally and internationally for his contribution to the field of nanoscale biomedical diagnostics and therapeutics in relation to a number inflammatory diseases including asthma, viral infections, traumatic brain injury (TBI) and cancers. He has received substantial extramural research support including awards from the NIH, DOA, ONR, Department of Veterans? Affairs and Florida Department of Health. In addition to the two international awards early in his academic career, he is the recipient of the USF biotechnology award, the Sigma XI award, TBTF Technology Leadership Award, Excellence in Research and Innovation award and Global Corporate award in Nanotechnology. He has contributed substantially to scientific literature including over 170 publications, some in very high impact journals such as Nature Medicine and journal of Clinical Investigation, and has >30 U.S. and foreign patents. He is a Fellow of the National Academy of Inventors and of the American Institute of Medical and Biological Engineering. In recognition of his contribution to the biomedical nanotechnology, he was inducted to the ?Florida Inventors? Hall of Fame? in 2014. In addition, he has devoted his efforts in training clinical fellows and graduate students in research and teaching at the VA hospital. Dr. Mohapatra has been a research investigator at the VA Hospital since 1996 and has been funded with the Merit Review Award focused on respiratory syncytial virus (RSV) infection since 1999. His lab has contributed substantially to the translation of new genomic approaches such as those involving small-interfering RNAs (siRNA) and microRNAS and emerging field of nanomedicine, with the premise that these technologies will aid in developing new methods for diagnosis and therapy of diseases afflicting Veterans. Current research activities to be supported by this RCS Award are as follows. Project #1. Develop new prophylactic and/or therapeutic approaches using novel nanoscale technologies, which are effective against both primary and secondary RSV infections, broadly useful in all age groups and inexpensive. His proposed merit review project (A1 revision to be submitted) aims to develop a simple, smart and scalable nanomicellar system that combines novel targets for viral fusion-, cellular antiviral- and replication-inhibitors. Project #2. Investigate the potential of a novel combinatorial therapeutic approach in a rat model of moderate TBI that includes (i) a treatment to reduce inflammation (local and systemic) using a nano-formulated siRNA against a recently discovered target, CCL20, and (ii) a second treatment to promote neuroregeneration by mesenchymal stem cell therapy. Project #3. Develop a novel cellomic-based personalized cancer treatment approach using a four-dimensional (4D) tumoroid culture platform. The assay can be used by itself or as an adjunct assay to currently practiced genomic testing, which predicts drug(s) that will be the most appropriate for the treatment of that patient?s cancer. These innovative applications of nanomedicine approaches taken together are expected to lead to high impact therapies for Veterans and other Americans in need. !